Endometriosis is a common gynecological disease with unknown etiology that can cause severe pain and infertility. Presently a non-invasive diagnostic test for endometriosis is lacking and thus the gold standard for diagnosis is dependent on laparoscopy. Due to the high cost and additional risk associated with laparoscopy and the absence of definitive diagnostic clinical symptoms, there is a 10-year average delay from onset of symptoms to diagnosis. Taken together, there is a huge need for a noninvasive diagnostic for endometriosis to decrease this long time to treatment. There is growing evidence of altered DNA methylation of specific genes and increased expression of DNA methyltransferases in patient endometrium. However, to date a global analysis of the DNA methylation status of endometrial tissue is lacking. We hypothesize that patients will have a global DNA methylation profile distinct from controls. Defining this profile will further the understanding of the pathophysiology of endometriosis and in so doing, will provide new targets to develop novel diagnostics and therapeutics. The overall goal of this project is to define the global methylation status in the endometrium of women with endometriosis and to use this knowledge to select markers for a novel diagnostic. While the long-term goal of this project is to develop a non-invasive diagnostic test for endometriosis, the specific goal of this application is to identify potential diagnostic targets. Specifically, global DNA methylation patterns of endometrial tissue from patients will be compared to those of disease free controls. A regression model will be used to identify those markers least affected by potential confounding factors. It is strongly anticipated that completion of the proposed study will provide a solid foundation for development of a novel, noninvasive diagnostic for endometriosis and have a sustained and powerful impact on patients with endometriosis. The proposed methodological approach lends itself to rapid translation of identified targets to a minimally or completely non-invasive, rapid diagnostic. The results of these studies will be used to significantly decrease the latency of diagnosis and thereby decrease the amount of time that patients suffer from pain and/or infertility. PUBLIC HEALTH RELEVANCE: It is currently not possible to diagnose endometriosis without surgery. This project will be the first to explore an important and thus far largely overlooked component. It is anticipated that the results of the proposed studies will be used to significantly decrease the time to diagnosis and thereby decrease the amount of time that patients suffer from this disease. Furthermore, the development of a non- or minimally-invasive diagnostic test for endometriosis will prevent unnecessary laparoscopies. Thus, by preventing unnecessary, expensive surgical procedures and providing an earlier diagnosis, this work will further reduce the cost associated with treating endometriosis.